title: Effects of sevoflurane on the expression of tau protein mRNA and Ser396/404 site in the hippocampus of developing rat brain.
abstract: BACKGROUND
  General anesthesia induces a transient hyperphosphorylation of tau protein that is associated with neurotoxicity in neonatal rats, but the mechanism remains unknown. The current study sought to investigate the effects of sevoflurane on the levels of tau phosphorylation at phosphor-Ser396/404 and total tau mRNA in the hippocampus of neonatal rats.
  
  
  METHODS
  Thirty-six 7-day-old rats were randomly exposed for 6 h to either 3% sevoflurane (S) or air (NC) as a placebo. They were sacrificed at 1, 7 and 14 days after the anesthesia, respectively, and thus assigned to S1d , S7d , S14d , NC1d , NC7d , and NC14d groups (n = 6). Their brain tissues were harvested and then subjected to histopathologic, Western blot and real-time polymerase chain reaction analysis.
  
  
  RESULTS
  Microtubule cytoskeletons were arranged in neat parallel rows in rats exposed only to air, whereas the microtubules were arranged in a disorderly and intermittent (nonparallel) fashion in rats exposed to sevoflurane. The levels of tau mRNA in the S1d and S7d groups were significantly higher than those in the NC1d and NC7d groups. There was no significant difference in the levels of tau mRNA between the S14d and NC14d groups. The levels of tau protein at Ser404 in the S1d , S7d, and S14d groups were significantly higher than those in NC1d , NC7d, and NC14d groups. The levels of tau protein at Ser396 in the S1d , and S7d groups were significantly higher than those in the NC1d , and NC7d groups, while there was no significant difference in the levels of tau protein at Ser396 between the S14d group and the NC14d group, respectively.
  
  
  CONCLUSIONS
  In rat hippocampus, sevoflurane was associated with microtubular disarray as well as increased levels of tau mRNA and excessive phosphorylation of tau protein at Ser396 and Ser404. This implicates that sevoflurane may induce neurotoxicity.
authors.affiliation: Department of Anesthesiology, The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Hu
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Jin
authors.forename: Li-li
authors.initials: LL
authors.lastname: Xu
authors.forename: Zhi-rui
authors.initials: ZR
authors.lastname: Zhu
authors.forename: Yi-lei
authors.initials: YL
authors.lastname: Jiang
authors.forename: Robert
authors.initials: R
authors.lastname: Seal
mesh_terms: D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001784:Blood Gas Analysis; D051360:Cyclin-Dependent Kinase 5 / Q000096:biosynthesis / Q000235:genetics; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012694:Serine / Q000235:genetics*; D000077149:Sevoflurane; D016875:tau Proteins / Q000096:biosynthesis*
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D012333:RNA, Messenger; D016875:tau Proteins; D000077149:Sevoflurane; D012694:Serine; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat; D038362:Glycogen Synthase Kinase 3
keywords: neonatal; phosophorulation; sevoflurane; tau